Thiol-protease inhibitors (cytoplasmic α- and β-TPIs; plasma α1- and α2-TPIs); Acid, neutral and basic cysteine-protease inhibitors (ACPI, NCPI and BCPI); Thiostatins
Cystatins were originally defined as endogenous inhibitors of thiol- or cysteine- proteases. Later, the discoveries of several proteins whose primary sequence revealed substantial homology to the typical cystatin domain led to the definition of a cystatin super-family. With the identification of other types of intracellular cysteine-proteases, however, it became clear that cystatins inhibit mainly cysteine-proteases present in endosomes and lysosomes. Additionally, many of the newer members of the cystatin super-family have less than 30% homology to classical cystatins and do not inhibit lysosomal cysteine-proteases. Moreover, several proteins with little apparent amino acid sequence homology fold into typical three-dimensional structures attributed to cystatins. Thus, the term “cystatins” now...